Flu Drugs Challenged in Full Data Review
Written by Editor   
Thursday, April 10, 2014 01:00 AM

Two major anti-influenza drugs have more limited benefits and greater risks than was previously thought, according to new reviews -- the first to have access to all the clinical trial data.  The reviews of the neuraminidase inhibitors oseltamivir (Tamiflu) and zanamivir (Relenza) are the culmination of several years of often-controversial research.  They call into question the value of the medications both as treatment and prophylaxis, the way drugs are currently approved, and decisions to stockpile the drugs at a cost of billions.

The reviews themselves are unprecedented: The drugmakers turned over thousands of pages of previously closely held corporate data on a host of studies. Taken together, the data show that "effectiveness has been overplayed and harms underplayed."

The major conclusions drawn from the reviews:

  • When used as a treatment, both drugs cut the time to the relief of symptoms -- by about 17 hours for oseltamivir and 14 hours for zanamivir.
  • When used as prophylaxis in people exposed to the flu, both reduced the risk of symptomatic disease but not asymptomatic infection and therefore would have little effect on the risk of transmission during a pandemic.
  • Oseltamivir caused nausea and vomiting and increased the risk of headaches, renal events (decreased creatinine clearance) and psychiatric syndromes (such as confusion and depression).
  • Zanamivir, an inhaled drug, was linked to cases of bronchospasm, but was mostly well tolerated, possibly because it has a low bioavailability.
  • Neither drug was shown to reduce the risk of hospital admission for flu, although there was a slight reduction in self-reported but unverified pneumonia among adults for both drugs.
  • For oseltamivir, the reviewers found it difficult to tease out any clinically significant effects on complications and viral transmission because of limited data and problems with study design.
  • Zanamivir had no effect on flu complications or the risk of death from influenza.

In particular, the findings undercut the rationale for stockpiling oseltamivir, according to co-author Peter Doshi, PhD, of the University of Maryland School of Pharmacy in Baltimore. The U.S. alone has spent more than $1.3 billion for oseltamivir, and other governments have also chipped in to a greater or lesser extent. All told, about $9 billion has been spent around the world for oseltamivir stockpiles -- half of Roche's $18 billion in profit since the drugs was launched in 1999.  The idea was that the drug would reduce the severity of illness but, more importantly, could be used to prevent transmission.

The drug was stockpiled because of concerns that the disease was catastrophic and this could help ameliorate the catastrophe.  But the clinical studies, he said, did not test that idea. "Mortality was not an endpoint of interest to them, hospitalizations were not an endpoint of interest ... because they never expected to see an effect in these areas."

The main problem with both drugs is a "creeping emphasis" that means they are being used more widely than they should be including in the hope of preventing bacterial complications.  Doctors know that the drugs reduce the symptomatic period modestly and that the drugs have to be given early in the disease course to have even that effect.  But most patients show up outside the period when the drugs will work "and yet we still give these particular medications.

Source:  http://www.medpagetoday.com/InfectiousDisease/URItheFlu/45184